The pathways linking gratitude to cardiovascular reactivity (CVR) to acute stress are not fully understood. We examine whether this association is mediated by social support. Healthy adults (N = 178) completed measures of trait gratitude and perceived social support and participated in a standardised mental arithmetic and speech stress testing protocol. Their CVR (i.e., systolic and diastolic blood pressure [SBP, DBP], heart rate [HR], cardiac output [CO] and total peripheral resistance [TPR]) were monitored throughout. Gratitude was positively associated with SBP, DBP and TPR reactivity, with those reporting higher gratitude showing higher CVR. Social support was positively associated with TPR to the maths task. The association between gratitude and TPR was mediated by social support but this was only evident in response to the maths task and not the speech task. These novel findings suggest that CVR may be a potential mechanism underlying the gratitude-physical health link.